Conditional Gastrointestinal Stimulation for Improved Motility

ABSTRACT

Systems and methods for gastrointestinal electrical stimulation to treat abnormalities in gastrointestinal motility are provided. In some embodiments, a system for relieving ileus includes an intraluminal catheter comprising: a catheter body having a proximal tip and a distal tip and a duodenal portion proximal to the distal tip of the catheter; and at least one electrode pair disposed along the duodenal portion of the intraluminal catheter, the at least one electrode pair being configured to detect a sensing information indicative of myoelectric activity of a patient and to provide stimulation energy; a sensing system in communication with the at least one electrode pair to receive the sensing information; and an energy delivery system in communication with the at least one electrode pair and the sensing system, the electrical energy delivery system being configured to delivery energy to the patient through the at least one second electrode pair based on the sensing information from the sensing system.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/933,555, filed on Nov. 5, 2015, which claims the benefit of andpriority to U.S. Provisional Application Ser. No. 62/075,687, filed onNov. 5, 2014, all of which are incorporated herein by reference in theirentireties.

FIELD

The present disclosure relates to systems and methods forgastrointestinal electrical stimulation to treat abnormalities ingastrointestinal motility.

BACKGROUND

Gastrointestinal (GI) motility plays an important role in the health andwell-being of persons of all ages. GI motility is one of the mostcritical physiological functions of the human gut. Without coordinatedmotility, digestion and absorption of dietary nutrients could not takeplace. To accomplish its functions effectively, the gut needs togenerate not just simple contractions but contractions that arecoordinated to produce transit of luminal contents (peristalsis). Thus,coordinated gastric contractions are necessary for the emptying of thestomach. Abnormalities in motility may lead to a variety of seriousdisorders, such as gastroparesis, Ileus, obesity, diarrhea,pseudo-intestinal obstruction, irritable bowel syndrome, and among manyothers. A need continues to exist for additional feasible and suitablemeans to treat GI motility disorders.

SUMMARY

The present disclosure provides systems and methods for gastrointestinalelectrical stimulation to treat abnormalities in gastrointestinalmotility.

In some aspects, there is provided a stimulation catheter that includesa catheter body having a proximal tip and a distal tip and a duodenalportion proximal to the distal tip of the catheter; and at least oneelectrode pair disposed along the duodenal portion of the intraluminalcatheter, the at least one electrode pair being configured to detect asensing information indicative of myoelectric activity of a patient andto provide stimulation energy. In some embodiments, the duodenal portionof the intraluminal catheter extends for between about 20 cm to 30 cmproximally from the distal tip of the catheter body. In someembodiments, the catheter may further include one or more pressuretransducers disposed along the duodenal portion.

In some embodiments, the catheter includes at least one first electrodepair configured to detect the sensing information and at least onesecond electrode pair configured to provide stimulation energy. The atleast one second electrode pair may be spaced apart from the at leastone first electrode pair by a distance of between about 1 cm to about 10cm. In some embodiments, multiple electrode pair spaced apart from oneanother may be provided to stimulate the bowel sequentially.

In some aspects, there is provided a system for relieving ileus thatincludes an intraluminal catheter comprising: a catheter body having aproximal tip and a distal tip and a duodenal portion proximal to thedistal tip of the catheter; and at least one electrode pair disposedalong the duodenal portion of the intraluminal catheter, the at leastone electrode pair being configured to detect a sensing informationindicative of myoelectric activity of a patient and to providestimulation energy; a sensing system in communication with the at leastone electrode pair to receive the sensing information; and an energydelivery system in communication with the at least one electrode pairand the sensing system, the electrical energy delivery system beingconfigured to delivery energy to the patient through the at least onesecond electrode pair based on the sensing information from the sensingsystem.

In some embodiments, the energy delivery system is configured to delivera single pulse of 100 msec at 4 mA in phase with natural electricalactivity. In some embodiments, the energy delivery system is configuredto deliver a pulse train of 20 hz at 1-10 mA in phase with naturalelectrical activity, with a pulse width of 2 msec and duration of 500msec. In some embodiments, the energy delivery system is configured todeliver between 12 to 30 pulses per minute out of phase with naturalelectrical activity, the pulses being of 20 Hz at 4 mA, with a pulsewidth of 2 msec and duration of 500 msec.

In some aspects, there is provided a method for treatment of gastricmotility issues that includes advancing an intraluminal catheter into astomach of a patient, the intraluminal catheter comprising: a catheterbody having a proximal tip and a distal tip and a duodenal portionproximal to the distal tip of the catheter; and at least one electrodepair disposed along the duodenal portion of the intraluminal catheter,the at least one electrode pair being configured to detect a sensinginformation indicative of myoelectric activity of a patient and toprovide stimulation energy; positioning the duodenal portion of theintraluminal catheter in a duodenum of the patient; causing a sensingsystem in communication with the at least one first electrode pair toreceive information from the at least one first electrode pair; andcausing an energy delivery system in communication with the at least onesecond electrode pair and the sensing system to delivery energy to thepatient through the at least one second electrode pair based on thesensing information from the sensing system. In some embodiments, thepatient may be monitored to determine a type of motility the patienthas, to determine whether to apply a synchronous electrical modulationif hypomotility is detected or to apply a inhibitory electricalmodulation if uncoordinated hypermotility is detected.

In some aspects, there is provide a method for treatment of gastricmotility issues that includes sensing information about motility of apatient from implanted at least one first electrode pair in a duodenumof a patient; determining a type of motility the patient has based onthe sensed information; and based on the determined type of motility,communicating with at least one second electrode pair in the duodenum ofthe patient to deliver an electrical modulation energy to the patient,wherein a synchronous electrical modulation is applied if hypomotilityis detected and an inhibitory electrical modulation is applied ifuncoordinated hypermotility is detected. In some embodiments, theelectrodes are contained within at least one capsule attached to a wallof duodenum. In some embodiments, such capsules include Bluetoothcommunication circuitry for communication with an external controllerfor sensing information.

BRIEF DESCRIPTION OF THE DRAWINGS

The presently disclosed embodiments will be further explained withreference to the attached drawings, wherein like structures are referredto by like numerals throughout the several views. The drawings shown arenot necessarily to scale, with emphasis instead generally being placedupon illustrating the principles of the presently disclosed embodiments.

FIG. 1 schematically illustrates an embodiment of a system of thepresent disclosure in operation.

FIG. 2 illustrates a catheter of the present disclosure in the stomachof a patient.

FIG. 3 illustrates a catheter of the present disclosure in the stomachof a patient.

FIG. 4A illustrates an embodiment of a catheter of the presentdisclosure.

FIG. 4B illustrates an embodiment of a balloon suitable for use with acatheter of the present disclosure.

FIG. 5 illustrates an embodiment of a catheter of the presentdisclosure.

FIG. 6 illustrates an embodiment of an introducer catheter of thepresent disclosure.

FIG. 7 illustrates an embodiment of an introducer catheter of thepresent disclosure.

FIG. 8 illustrates a cross section of an introducer catheter of thepresent disclosure.

FIG. 9 illustrates an embodiment of an intestinal electrical stimulationdevice of the present disclosure.

FIG. 10 is a flow chart for determining an output mode of a stimulatorof the present disclosure.

FIG. 11 illustrates an embodiment of a stimulation system of the presentdisclosure.

FIG. 12A, FIG. 12B, and FIG. 12C present a schematic representation ofoperation of the gastrointestinal track.

FIG. 13 illustrates an embodiment of a catheter of the presentdisclosure.

FIG. 14 illustrates an embodiment of a catheter of the presentdisclosure.

While the above-identified drawings set forth presently disclosedembodiments, other embodiments are also contemplated, as noted in thediscussion. This disclosure presents illustrative embodiments by way ofrepresentation and not limitation. Numerous other modifications andembodiments can be devised by those skilled in the art which fall withinthe scope and spirit of the principles of the presently disclosedembodiments.

DETAILED DESCRIPTION

Systems and methods are described to provide stimulation to the stomach,small bowel (duodenum, jejunum, ileum) and the large bowel (colon) toenhance intestinal or gastric motility or other neurological responsesand to enable patients with motility issues to take in nutrition orallyor enterally (through a feeding tube). The systems and methods of thepresent disclosure may be used to treat motility issues caused by avariety of conditions, including, but not limited to, ileus, diarrhea,gastroparesis, short bowel syndrome, pseudo-intestinal obstruction,constipation or similar conditions. In some embodiments, the systems andmethods of the present disclosure may be used to treat obesity,diarrhea, pseudo-intestinal obstruction, irritable bowel syndrome,ileus, gastroparesis, and constipation or for regulating appetite. Oraland enteral feeding may further stimulate normal motility of the GItract. Stimulation is provided through an intra-luminal catheterconnected outside the patient to a smart generator or via an implantedsensor/stimulator capsule attached to the bowel walls and eitherautonomously or remotely accessed. Uses include restarting of normalbowel motility following ileus caused by surgery, sepsis and otherwell-known causes of ileus and the prevention of ileus when usedperi-operatively or immediately post-operatively. In some embodiments,the systems and methods of the present disclosure allow sequentialpacing down the duodenum. In some embodiments, the systems and methodsof the present disclosure allow stimulation of one location whilerelaxing or inhibiting an adjacent location.

When a patient presents with ileus, his or her symptoms may includenausea, bloating and vomiting which results in the inability of thepatient to tolerate enteral feeding. Ileus typically occurs followingabdominal surgery but may also occur as a result of trauma, infection,opioid use and many other causes. In some embodiments, a catheter isplaced through either the nose or mouth, through the stomach and pylorusand into and through much of the duodenum, sometimes into the jejunum.Guidance of this catheter may be via visualization (endoscopic),radiologic, ultrasound, magnetic or other means. The catheter mayinclude electrodes or electrode pairs that are used to sense theelectrical activity of the duodenum and to subsequently provideelectrical stimulation. The catheter may also include pressuretransducers or channels for fluid to be connected to external pressuregauges. These pressure gauges may be used to monitor peristalticactivity of the GI tract more accurately than by electrical means,although electrical monitoring may be sufficient.

An initial monitoring period may be anywhere between 5 minutes andseveral hours (for example, 4 hours). In some embodiments, about 30minutes may be used to determine if the cause of the ileus is a resultof hypomotility, reduced or no contractions, or uncoordinatedhypermotility, excessive and uncoordinated contractions. Using thisinformation, the type of stimulation can be determined and deliveredthrough the electrode pairs. Synchronous Electrical Modulation (SEM) maybe provided if the ileus is caused from hypomotility. InhibitoryElectrical Modulation (IEM) may be provided if the ileus is caused fromuncoordinated hypermotility. In some embodiments, SEM pulses areprovided in synchronization with natural slow waves at a rate of up to12 pulses per minute (ppm) in the duodenum, which corresponds to thenatural frequency of slow waves in the duodenum. IEM is asynchronous andmay be provided at a rate greater than the natural frequency or over12ppm in the duodenum, to interfere with natural contractility. Thisnatural frequency of contraction varies from 3 ppm in the stomach to 12ppm in the duodenum, 11 ppm in the jejunum and 8 ppm in the ileum.

In some embodiments, the initial stimulation may last between about 5minutes and several hours (2 hours, for example). In some embodiments,after about 60 minutes of electrical stimulation, stimulation is stoppedand natural activity is measured with either the electrodes and/orpressure gauges for about 5-120 minutes or about 30 minutes. If naturalmotility does not occur, the stimulation is repeated. Migrating MotorComplex (MMC) occurs roughly every 2 hours so this period of treatmentmay help to mimic natural activity. During the first or the secondapplication of stimulation, liquid nutrition may be introduced throughthe stimulation catheter into the intestine. The presence of nutritionin the small bowel itself may have a stimulating effect oncontractility. As the nutrition moves distally in the small bowel, itmay enhance additional peristaltic response of the distal small bowel.The goal of this therapy is to permit oral or intestinal feeding withoutthe need for the electrical stimulation.

In reference to FIG. 1, in some embodiments, the conditionalgastrointestinal stimulation system of the present disclosure includesan introducer or delivery catheter, an intraluminal stimulation catheter104 and an external controller 102.

A stimulation catheter 104 may be placed during the surgical procedureand the appropriate stimulation applied while the patient is undergoingsurgery. By doing this, the intestine may be prevented from entering theileus state which may speed recovery of the patient following surgery.The stimulation catheter 104 may also be placed through either agastrostomy tube through the stomach wall to the small intestines orthrough a colostomy tube to the colon. In these cases, the catheter maybe left in place to treat more chronic conditions such as gastroparesisand constipation. Typically, the catheter may be placed following thesurgical procedure once the ileus is identified. A portable controllerand battery pack may be carried for instance around the waist or may besuspended from an IV pole or a bed. The stimulation catheter 104 may bepassed through the nose of the patient, through the esophagus, stomach110, duodenum and sometimes into the jejunum 112.

The stimulation catheter 104 includes a plurality of electrodes 106 tobe placed mainly in the duodenum. These electrodes 106 may connectproximally to a sensing and stimulation controller 102. The stimulationcatheter may include a side branch 100 for injecting feeding solutions,withdrawing fluids and gasses and connecting pressure transducer lumensto readouts.

As shown in FIG. 1, when the stimulation catheter 104 is placed, theelectrodes of the stimulation catheter 106 pass through the stomach 110and reside in the duodenum 108. It may be beneficial to place thiscatheter completely through the duodenum 108 and into the jejunum 112,however, other placements are also possible. The duodenum is typicallyabout 30 cm in length from the pylorus 114 to the ligament of Treitz 116where the jejunum begins. Placing the catheter 104 beyond the ligamentof Treitz may reduce the likelihood that the catheter is pulled backtowards the stomach. In some embodiments, the catheter is sufficientlylong to pass through the nose or mouth, the esophagus, the stomach, theduodenum and perhaps 10 cm into the jejunum. The overall catheter lengthmay be about 150 cm to about 300 cm. In some embodiments, the cathetermay be about 240 cm long. For chronic applications, the catheter couldbe placed through a PEG tube in the stomach wall. This would require ashorter catheter of between about 100 and about 200 cm or about 150 cm.

The catheter 104 may have at least two sets of electrodes 106 locatedbetween about 10 cm to about 30 cm from the pylorus, or at about 15 cmfrom the pylorus. As the distal end of the catheter would typically belocated at the ligament of Treitz, which is about 30 cm from thepylorus, these electrodes may be located at about 10-20 cm from thedistal end of the catheter. The catheter may have a bump or line locatedat between about 30 cm and about 35 cm from the distal end or, in someembodiments, at about 33 cm from the distal end. This bump or line canbe used to align with the stomach side of the pylorus when the catheter104 is in the proper position. In some embodiments, the portion of thecatheter to be placed in duodenum (or duodenum portion) is between about20 cm to 30 cm long. The duodenum portion may start at the distalterminal of the catheter or may be proximally set back by about 2 cm to3 cm. In some embodiments, fluoroscopy may be used to visualize theelectrodes to ensure they are about midway through the duodenum when inthe proper placement. In some embodiments, the more proximal electrodepair may be used for sensing electrical activity of the duodenum, whilethe more distal pair may be used for passing electrical energy into thewall of the duodenum to stimulate the enteric nerves and/or smoothmuscle. However, this configuration may be reversed.

In some embodiments, a single pair of electrodes can be used, which canelectronically be switched from a sensing mode to a stimulating mode. Insome embodiments, multiple pairs of electrodes for sensing and multiplepairs of electrodes for passing electrical energy. As noted above, insome embodiments, the proximal electrodes may be dedicated to sensingand the distal electrodes to stimulation, but such order may bereversed. In some embodiments, the electrodes may be positioned at about10 to about 20 cm from the distal tip.

The electrodes of each electrode pair may be isolated from each other(bipolar). The electrodes may be made from platinum, iridium, stainlesssteel or other electrically conductive and biocompatible materials. Insome embodiments, the electrodes may also be made from conductive andbiocompatible wire that is wrapped around the circumference of thecatheter multiple times. Wires are connected from each of the electrodesto the proximal end of the catheter which exits the patient.

As shown in FIG. 8, in some embodiments, electrode wires are run throughlumens in the catheter to connect electrodes to the sensing system andthe energy delivery system. Multiple lumens may be extruded into thecatheter for the electrode wires or the wires may be run through thecentral lumen. The electrodes may be mechanically, adhesively orthermally bonded to the catheter wall and exposed so that contactbetween the electrode and the bowel mucosa is ensured. The electrodesmay be 2-7 mm in width or about 5 mm. Each electrode pair may beseparated by a space of 3-15 mm or about 5 mm. Each set of electrodesmay be separated by a space of about 1-10 cm or about 3 to 5 cm. Morethan one stimulation electrodes, for example, between 2 and 5, may beplaced distal to the sensing electrodes on the catheter to betterstimulate the bowel sequentially in a proximal to distal fashion tomimic peristaltic waves.

In some embodiments, the sensing electrode may be disposed between about15 cm to 20 cm from the distal end of the catheter, and the stimulationelectrodes may be disposed between about 3 cm and about 12 cm from thedistal tip. In some embodiments, multiple stimulation electrodes may bedisposed at about 12 cm, 9 cm, 6 cm and 3 cm from the distal tip of thecatheter. In some embodiments, multiple sensing electrodes may be used,and such electrodes may be placed between the stimulation electrodes.

In some embodiments, additionally or alternatively to electrode pairs inthe duodenum, one or two electrode pairs may be positioned at about 5 cmto about 10 cm proximal to the pylorus in the antrum or the greatercurvature of the stomach. These electrodes can be used to sense andstimulate stomach contractions. In some embodiments, these electrodesmay start at between about 38 cm and about 43 cm from the distal end ofthe catheter and progress proximally such that the stimulationelectrodes would be between about 38 cm to 50 cm from the distal tip ofthe catheter and the sensing electrodes would be placed about 3 cm toabout 10 cm proximal to the stimulation electrodes.

In some embodiments, as shown in FIG. 13, each electrode may becontrolled separately from other electrode in electrode pairs. In someembodiments, electrodes are spaced evenly about 1 to 5 cm apart withbetween 10-20 electrodes down the length of the catheter such that allelectrodes lie within the duodenum. In some embodiments, electrodes maystart at about 10 cm to 15 cm from the distal tip and then be placed onthe catheter every 1 cm to 2 cm. In some embodiments, such electrodesmay be placed at about 15, 14, 13, 12, etc. cm from the distal end ofthe catheter. In some embodiments, these electrodes may be used as dualpurpose electrodes, both for sensing and stimulation. With a series ofelectrodes, sequential stimulation of the duodenum may be performed byactivating the electrodes from the proximal to the distal end, switchingthe polarity of each electrode as one goes distally.

In some embodiments, as shown in FIG. 14, the catheter may be madeslightly longer, by at least 40 cm, which would therefore besufficiently long as to have its distal end at least 10 cm in thejejunum. The distal set of stimulation electrodes may be thus being inthe jejunum.

In reference to FIG. 4A, the catheter 400 may be sufficiently stiff toprevent its kinking or pulling back into the stomach, but may besufficiently flexible to enable passage through the duodenum withouttrauma. The diameter of the catheter 400 may be about 5 mm (3-7 mm). Thecatheter may be fabricated from PVC, polyurethane, silicone or otherbiocompatible polymers. The catheter may have a central lumen 404 ofabout 2 mm (1-3 mm) diameter that runs the length of the catheter to itsdistal end. The central lumen may be used to either evacuate contents ofthe bowel or to deliver nutrition in the form of liquid nutrients to thebowel. Electrode wires may also be passed through the central lumen. Insome embodiments, additional lumens may be provided for passage of theelectrode wires to the proximal end or as pressure taps or the wires maybe passed through the central lumen.

In some embodiments, the catheter is configured to ensure contactbetween the electrodes and the bowel mucosa to ensure transmission ofstimulation and sensing electrical energy. In some embodiments, thecatheter may be specifically shaped along its length to ensure contactbetween the bowel mucosa and the electrodes. For example, the cathetermay have a spiral/corkscrew shape as shown in FIG. 5, S shape or asimilar shape. In some embodiments, the shape could be thermally setinto the catheter shaft if the catheter is made from a thermoplasticpolymer such as urethane or nylon. In some embodiments, a wire with apre-determined shape may be embedded or removal inserted into thecatheter shaft, forcing the catheter to take the shape of the wire. Thediameter of the spiral may be about 10 cm to about 25 mm for the smallbowel and about 10 mm to about 50 mm for the large bowel. As shown inFIG. 5, catheter 502 may be placed in intestine 500 with multiple coils506 causing electrodes 504 to engage the intestine wall.

FIG. 2 illustrates the catheter 202 having electrodes 206 in the stomach212 as the catheter is being passed into the intestine 210. In someembodiments, to ease passage of the catheter 202 through the intestine210, a ball or balloon 208 may be attached to the distal end of thecatheter. If a balloon is used, the balloon may be inflated with wateror air prior to advancing it through the bowel. The balloon or ballserves as an atraumatic bumper to resist perforation of the bowel. Theballoon may have a minimal distal tip. The balloon may be made of acompliant material such as latex rubber, silicone or urethane, or may benon-compliant if made of stiffer materials such as PET. The balloon maybe about 8-15 mm in diameter when inflated and may have a small profileupon collapse to allow the catheter to pass through any introducercatheters 204 that might be used to enable passage through the stomach.A lumen may be fabricated through the catheter to serve as an inflationlumen for the balloon. If a ball is used, the ball may also be about8-15 mm in diameter. The ball may be permanently attached to the distalend of the catheter, or may be remotely disengaged. The ball may bedesired to make the distal ball from a radiopaque material such astitanium dioxide or barium filled plastics, to enable tracking withfluoroscopy or to embed a metal marker.

In some embodiments, one or more pressure measuring devices may bedisposed at various locations along the length of the catheter. Thesepressure measurements may be used to detect the presence of peristalsisin the GI tract and may be located between electrodes or electrodepairs. Solid state pressure transducers such as those made by Millar(MikroCath) or MedKinetic (Ningbo China), strain gauge, piezoelectric orother transducers may be bonded to the catheter. In some embodiments,holes in the catheter may be cut or drilled that connect to lumensrunning the length of the catheter. These lumens may be filled withwater and then connected to external pressure transducers. Pressuremeasurements may be desired at 1 to 20 locations along the length of thecatheter. In some embodiments, 4 to 8 locations adjacent to thestimulation electrodes may be employed. If only 1 pressure transducer isused, it may be located at about 10-15 cm from the distal end of thecatheter. It is also possible to monitor peristalsis with electricalactivity alone thereby eliminating the pressure transducers.

The pressure measurement locations may be adjacent to the stimulationelectrode pairs or mounted on top of the electrodes. If water manometryis used, the holes may also be used to infuse small amounts of nutrientsolution when the electrode is in the SEM mode to synchronizeperistalsis with feeding. The presence of nutrients in the small bowelmay provide additional peristaltic stimulation. The ability tocoordinate nutrient delivery at the contraction site may better achievethe ultimate goal of enhanced nutrition and improved peristalsis thancurrent devices or than either therapy alone.

A hole in the catheter that connects with a lumen in the catheter may belocated within the stomach to permit suctioning of food or gas from thestomach to keep the patient comfortable until peristalsis initiates.This hole may be located about 45-70cm from the distal end of thecatheter.

Introducer Catheter

In some embodiments, the introducer catheter system may be employed topermit easy and safe advancement of the stimulation catheter through theanatomy to the duodenum and jejunum. This may be done without anyadditional special instrumentation, but may also be assisted using imageguidance devices such as ultrasound, fluoroscopy or endoscopicvisualization. In placing feeding tubes, there is a risk that the tubeis placed into the trachea instead of the esophagus. Also, placingfeeding tubes past the pylorus can be difficult. The system describedherein is intended to simplify placement.

Direct visualization may be used to enable the user to observe that thetube is in the correct lumen (esophagus). In reference to FIG. 4A andFIG. 4B, in some embodiments, a small endoscope 402 may be fabricated topass through the central lumen 404 of the stimulation catheter. Theendoscope may be either a fiber or electronic scope and may be 1-3 mm indiameter. If the endoscope is a chip type electronic camera with a lensand LED's used for light at its distal end 408, then wires may be routedthrough the central lumen of the stimulation catheter and connected tothe external power source and a simple display unit. This endoscope maybe reusable or disposable.

In reference to FIG. 3, when introducing a catheter 304 into and throughthe stomach, the greater curvature of the stomach 300 may be used as aguide. A catheter may follow the greater curvature, which may guide thecatheter towards the pylorus 302. To push the catheter through thepylorus, and to prevent kinking of the proximal shaft 304, among otherbenefits, a proximal portion of the catheter may be stiffened. Thiscould be done by advancing a stiff metal or plastic core 410 down theinner lumen of the catheter, as shown in FIG. 4A. In some embodiments,an over sheath 204 may be advanced over the outside of the catheter 202for the portion of the catheter that resides in the stomach 212, asshown in FIG. 2. In some embodiments, this stiff shaft or sheath mayremain in the stomach 212, and would not be advanced through thepylorus.

An additional challenge can be to align the catheter 304 with thepylorus 302. Sometimes the catheter may hit the lower edge of thepylorus and not track through it. Deflection mechanisms may be builtinto the catheter such as off-center pull wires. In some embodiments, awire may be run through a lumen 312 in extrusion 310 to the distal endof the catheter and attached at the distal end of the catheter withadhesive or other means. When this wire is pulled at its proximal end,it forces the distal end to curve towards the wire making the cathetersteerable. Multiple lumens and wires around the catheter may be used forsteering in multiple axes.

In some embodiments, a balloon 306 may be mounted to the distal end ofthe catheter, which may also be used to track through the duodenum, maybe inflated in the stomach. This inflation may deflect the tip of thecatheter 308 off the pyloric ledge and ease advancement into thepylorus.

In some embodiments, as shown in FIG. 4A and FIG. 4B, a segmentedballoon may be employed. Such segmented balloon 406 may be disposedaround the catheter. In some embodiments, a balloon segment that isinflated can help push the catheter away from the stomach wall. By wayof a non-limiting example, as shown in FIG. 4B, the segmented balloon406 may have four segments 1-4, but more or less segments may be used.In some embodiments, only one segment may be inflated making the profilesmaller for passage through the pylorus.

Instead of or in addition to passing an endoscope through the centrallumen of the stimulation catheter, as described above, visualization maybe incorporated into the introducer catheter as shown in FIG. 6. Thevisual introducer may be first advanced through the esophagus into thestomach. The visualization can be used to ensure the tube is goingthrough the esophagus and is positioned just at the pylorus. Thestimulation catheter may then be introduced through the visualintroducer, through the pylorus. Once in place in the duodenum, thevisual introducer may be removed from the patient. This may be reusableor disposable. FIG. 7 shows the scope and light source passing throughlumens in the wall of the visual introducer. An exemplary extrusioncross section is shown in FIG. 8 for this visual introducer devicedescribed in FIG. 7.

Stimulation Parameters

One of the goals of SEM is to generate contractions within the smallintestine. In this method, each stimulus is synchronized with intrinsicmyoelectrical activity. The SEM signals are believed to trigger theenteric nervous system to both contract and relax the small bowel. Insome embodiments, the SEM parameters may be a single pulse of betweenabout 50 msec to about 300 msec, in some embodiments, between about 75msec and about 125 msec, at between about 1 and about 10 mA, in someembodiments, between about 4 mA and about 6 mA, in phase with naturalelectrical activity peaks or, if no activity is present, at 12 ppm(pulses per minute) in the duodenum.

In some embodiments, pulse trains may be used of between about 5 andabout 100 hz, in some embodiments, between 15 hz and 25 hz, with a pulsewidth of between about lmsec and about 15 msec, in some embodiments,between about 2 msec and about 4 msec, and duration of about 50 to about500 msec, in some embodiments, between about 75 msec and about 125 msec.Such pulse trains may be delivered at about 1 mA and about 10 mA, and insome embodiments, between about 4 and about 6 mA.

In some embodiments, IEM may reduce the tone and tension of the smallbowel to allow nutrients to pass through the small intestine withreduced resistance. This may be accomplished by stimulating the bowelout of phase with natural myoelectrical activity by stimulating at over12 ppm (in the duodenum) at between about 15 ppm and about 30 ppm, insome embodiments, between about 18 ppm and 22 ppm, with parameterssimilar to those described above.

If there is one electrode pair on the catheter, then it is stimulatedper above. If multiple pairs of electrodes are present, the may bestimulated from the proximal to the distal end in sequence with a phaseshift (time delay between electrode pairs) that is present under normalconditions. In some embodiments, cycles of both SEM and IEM may beincorporated simultaneously in differing portions of the intestine. Forexample, when a proximal stimulation electrode pair is in SEM, a moredistal electrode pair may be in an IEM mode, or vice versa. In someembodiments, both gastric excitation (SEM) and inhibition (IEM) may beincorporated with coordination such that the duodenum is activated whenthe stomach is inhibited and vice versa.

External Controller

The external controller takes input from the pressure sensors and/orelectrical sensors and determines what type of contractile pattern ispresent. In some embodiments, this is done via peak detection. Ifhypomotility is detected, then the appropriate SEM signal is sent to thestimulation electrodes. If multiple electrodes are used, thenstimulation occurs from the proximal to the distal electrode.

System for Delivery of Intestinal Stimulation

The entire system may be composed of an intraluminal catheter (i.e.stimulation catheter as described above), an intestinal electricalstimulation (IES) device and a personal computer (PC). FIG. 9illustrates an embodiment of an IES device. The IES device may beconfigured to receive and amplify contractile (pressure) andmyoelectrical signals from a patient via the stimulation catheter,communicate with the PC (control unit) to determine the mode and patternof (IES) and deliver the stimulation to the small intestine of thepatient via the stimulation catheter. During the treatment, thestimulation catheter may be placed into the proximal small intestine todeliver IES to the small intestine. Intestinal contractions can bemeasured by the system and displaced on the PC.

In reference to FIG. 10, the output mode of the stimulator can bedetermined as follows:

-   -   a. If the recorded intestinal contractions during the past 30        min (or any other desired time period) are normal, EM does not        need to be performed.    -   b. If intestinal contractions are hypotensive (myopathy), SEM        may be delivered, i.e., each electrical stimulus may be        delivered at the detection of an intestinal slow wave peak        (measured by the EMG amplifier).    -   c. If intestinal contractions are hypertensive and uncoordinated        (neuropathy), IEM may be performed with parameters known to        inhibit intestinal contractions.

Whether EM is delivered or not, the intestinal contraction may becontinuously measured and their pattern may be assessed every 10 minutes(or any other desired time period) and a new decision for SEM or IEM orno stimulation is made.

Functionally, the IES system can be classified into measurement, controland stimulation units. In some embodiments, the measurement unit mayinclude an EMG amplifier and a manometric system; the control unit mayinclude a PC and data transmission among different modules; and thestimulation unit may be configured to deliver specific electrical pulse.

Manometric System: In some embodiments, the IES system may include amulti-channel manometric recording unit depending on the number ofpressure transducers located on the catheter. This unit is used torecord intestinal contractions of a patient. In some embodiments, asdescribed above, the stimulation catheter may include side holes and awater perfusion system and an amplifier. In some embodiments, solidstate pressure sensors may be placed on the catheter. In someembodiments, a manometric system may be incorporated in the stimulationcatheter.

EMG amplifier: The EMG amplifier may be used to amplify intestinalmyoelectrical activity. In some embodiments, a stand-alone 4 channel EMGamplifier can be used. In some embodiments, a one channel EMG amplifiercan be integrated into the IES device. The recorded intestinalmyoelectrical activity (slow waves) can be used to trigger stimulationwhen SIES mode is selected.

Control unit. The unit may be composed of a PC and data transmission,and is used to control the mode of IES. Some functions of the controland data transmission unit are as follows: a) to facilitate datatransmission among different modules in the device via internal highspeed data bus. For example, this unit can take measurement data fromthe manometric and EMG amplifiers and temporarily store them in thememory during the analysis process, and send these data to the PC fordisplay and permanent storage; b) to analyze the intestinal contractiledata using the algorithm obtained from the PC and to determine thepattern of intestinal motility; c) to determine the output mode of thestimulator according to the pattern of intestinal motility; and d) todetect the peak of each intestinal slow wave and use it to trigger theoutput of the stimulator when the stimulator is working in the mode ofsynchronized IES.

Several algorithms can be developed and stored on the PC, including thefollowings 1) software for the analysis of intestinal contractions; 2)algorithm for the selection of IES mode; 3) algorithm for detection ofslow wave peak.

Stimulation unit (pulse generator): The stimulation unit may be used toperform inhibitory IES (IIES) or synchronized IES (SIES). Amicro-stimulator may be used to generate universal wave forms, includingpulse trains that will be used for EM. In the mode of SEM, each stimulusoutput can be triggered by the detection of each intestinal slow wavepeak. By way of a non-limiting example, the following parameters may beused: train on-time of 0.5 s, off-time of 1.5 s, frequency of 20 Hz,pulse width of 2 ms and amplitude of 4 mA. The stimulation unit can bedesigned to have the following capacities: train on- and off-time of0-10 min, frequency from 0.05 Hz to 200 Hz, pulse width from 10 μs to600 ms (depending on frequency) and amplitude up to 20 mA.

Remote Stimulation

In reference to FIG. 11, in some embodiments, systems and methods areprovided for stimulating the intestine 1100 with a remote system. Thesensor/stimulator capsule 1118 may be attached to the wall of theintestine 1100 using various mechanical means, such as staples 1106. Insome embodiments, a coil could be screwed into the tissue or a barbcould be advanced into the tissue. In some embodiments, thesensor/stimulator capsule 1118 can be embedded into tissue 1104 of theintestine 1100 or adhesively bonded to the mucosa or submucosa. Thesensor/stimulator capsule 1118 may be delivered through a catheter 1108with a pusher mechanism 1112 and plate 1110. The sensor/stimulatorcapsule 1118 may be loaded into the catheter which is advanced into theintestine as described above. This may be done during surgery. Whenlocated in the desired position in the intestine, the pusher isadvanced, pushing the sensor/stimulator capsule 1118 from the catheter.The attachment means, in this case staples 1114, are loaded such thatthey are flat when inside the catheter. They may be made of Nitinolmetal and pre-shaped as shown in 1116. These attachment means may bestaple or hook-like taking advantage of either the superelastic or shapememory properties of Nitinol. As the sensor/stimulator capsule 1118 ispushed distally out of the catheter, the staples form and grasp theintestine wall. This attachment is likely to be good for 5-30 days,after which the intestines will push the device out and it will passthrough the GI tract normally and be excreted. Errodable polylacticacid, or equivalent polymeric attachment means between the anchors 1116and the capsule 1118 may enhance control over attachment duration. Insome embodiments, the entire attachment barb or staple could be made ofa biocompatible erodible or resorbable material permitting timedrelease. In some embodiments, the barbs could be retracted by amechanical device such as a motor and screw mechanism in thesensor/stimulator capsule 1118 thus releasing the attachment. In someembodiments, tissue adhesive could be used in patches to secure thesensor/stimulator capsule 1118 to the lumen wall or could be excreted bythe sensor/stimulator capsule 1118 at the appropriate location. Thesensor/stimulator capsule 1118 may also be delivered manually duringsurgery through the stomach or intestine. The sensor/stimulator capsule1118 may also be used in the colon to treat constipation.

The electrodes 1102 contact the mucosal tissue 1104. These electrodesmay measure the electric potential with respect to ground or to theother electrode(s) on the device. They therefore receive electricalsignals from the intestine such that the natural electrical activity ismeasured. These signals are analyzed in the capsule 1118 with internalcircuits to determine the optimal stimulation parameters needed tostimulate peristalsis. The same, or other, electrodes 1102 are then usedto provide electrical energy (under voltage or current control) to thewall of the intestine to provide the appropriate stimulations to causeperistalsis. The stimulation waveforms are typically pulsatile, bipolar,charge-balanced waveforms, but could be unipolar and not charge-balancedif hyperpolarization (inhibition) is desired. Waveforms may be deliveredin a pulsatile fashion.

In some embodiments, the circuit may be controlled by an externalcontroller which is coupled to the sensor/stimulator capsule 1118 by RFwith a coil placed on the outside of the patient's abdomen. Thesensor/stimulator capsule 1118 may have a tail 1120 on either or bothsides of the capsule which may serve as an antenna to transmit data onperistaltic activity to a receiver outside the body. For datatransmission, the capsule may contain an integrated circuit thatcontains a Bluetooth®, low energy, “system-on-a-chip” connected to theantenna. Alternatively, radio frequency chips and antennae may also beused. For energy transmission from the outside to the inside of thebody, the capsule may contain an inductive charging coil and chargingcircuitry which is inductively matched to an external coil placedagainst the skin.

In some embodiments, the barbs in the duodenum may be deployed bycovering the sensor/stimulator capsule 1118 and barbs in a material thatdissolves at elevated pH such that the prongs or barbs are held normallyflat. This sensor/stimulator capsule 1118 may be ingested prior tosurgery. Upon reaching the elevated pH of the duodenum, the coating maydissolve and the prongs exposed to the duodenal wall thereby engagingthe wall. Coatings may include methyl acrylate, cellulose, alginate andother polymers. In some embodiments, a pH sensor may be incorporatedinto the sensor/stimulator capsule 1118. Upon measuring elevated pH, thepH sensor could activate a motor to screw a corkscrew into the intestineor it could activate a heating circuit that would heat a shape memorymetal holder to release the barbs.

The sensor/stimulator capsule 1118 may contain batteries, at least 2electrodes and a circuit board with both active and passive components.The circuit board could contain a microprocessor or dedicated circuit toperform signal processing and stimulation. Upon deployment in theduodenum, the sensor/stimulator capsule 1118 may sense the myoelectricactivity and trigger pulses as needed. It may also transmit data outsidethe body.

Communication with the sensor/stimulator capsule 1118 from the outsideof the body may be made to measure pH, myoelectrical activity, pressurefrom a solid state pressure transducer. Also, communication may be madefrom the outside to the sensor/stimulator capsule 1118 to have it deployanchors at specific time or location, release anchors, start or stopstimulation.

Pattern of EM:

In some embodiments, alternating excitatory and inhibitory currents canbe applied in a progressive manner so that in effect peristalsis issimulated. This may also induce the same impact in the adjacent smallbowel. In some embodiments, bolus feeds may be applied and synchronizedin between the rings to coincide with “propulsive” currents.

In some embodiments, the pulse width of the stimulation used is greaterthan most neural stimulation waveforms. This may aid in stimulation ofboth the enteric nerves and the smooth muscle in the intestinal wall.For example, while the typical nerve stimulation waveforms have a pulsewidth of microseconds, in some embodiments of the present disclosure thepulse width is 50-300 msec.

In reference to FIG. 12A, FIG. 12B and FIG. 12C, movement of foodthrough the GI tract is controlled by several complex neural andhormonal mechanisms. These control mechanisms are both local andsystemic in their expanse. The enteric nervous system which runs thelength of the GI tract is said to be our second brain. The Interstitialcells of Cajal (ICC) serve as electrical pacemakers in the intestinesand create the bioelectrical slow wave potential that leads tocontraction of the smooth muscle. Electrical slow waves spread from ICCto smooth muscle cells and the resulting depolarization initiatescalcium ion entry and contractions. Slow waves organize gut contractionsinto phasic contractions that are the basis for peristalsis. Spikeelectrical potentials superimpose on slow waves and correspond to musclecontractions. Small intestine slow waves originate from the proximalduodenum and propagate as an annular wave front distally.

Although the exact causes of ileus are not known, ingestion of opioidsand inflammation and resulting disruption of enteric nerve stimulationhave been implicated. This can take the shape of reduced slow waves,reduced spikes or uncoordinated slow waves. Therefore, stimulating theenteric nerves directly with an intraluminal catheter as disclosedherein is likely to overcome local pathology and reset normalperistalsis.

In some embodiments, using a wider pulse may be useful to stimulate awider area. This may allow impacting a defect regardless of whether thedefect is the enteric nerves or the smooth muscle cells.

In some embodiments, the nerve stimulation as described herein may beused to reduce inflammation, which may in turn cause the ileus. Onemechanism of achieving this is through the inhibition of the sympatheticnerve activity and IL6 activity.

In the ICU setting, ileus may be more complex than in the post-operative(POI) setting. ICU patients may have more problems that could impactileus including sepsis. In POI, the combination of electricalstimulation and concurrent feeding should have a rapid impact onreversing ileus. In the ICU, the stimulation catheter may be left inlonger, perhaps days, maintaining stimulation and feeding until theunderlying problem resolves.

EXAMPLES

The following non-limiting examples of the systems and methods of thepresent disclosure are merely representative and should not be used tolimit the scope of the present disclosure. Large varieties ofalternative designs exist for the systems and methods and are within thespirit and the scope of the present disclosure. The selected examplesare therefore used mostly to demonstrate the principles of the methodsand devices disclosed herein.

Example 1

Intraluminal intestinal electrical modulation can completely entrainintestinal slow waves in dogs.

Aim: To investigate the feasibility of intraluminal intestinalstimulation and compare the effects to serosal stimulation.

Methods: Nine healthy hound dogs were used for this experiment. Fourpairs of electrodes were implanted on the serosa of the jejunum at aninterval of 5 cm with the most proximal pair 35 cm beyond the pylorus.An intestinal fistula was made 20 cm beyond the pylorus. Followingrecovery, simultaneous recordings of intestinal myoelectrical activitywere made for 2 hrs in the fasting state from both intraluminal andserosal electrodes. Various electrical stimulation parameters weretested.

Results: The frequency of the intestinal slow wave recorded from theintraluminal electrodes was identical to that from the serosalelectrodes 18.7±0.3 cycles/min vs. 18.7±0.3 cpm (r=0.99, p<0.001), aswas the percentage of normal 17-22 cpm waves (95.8±3.9% vs. 98.1±1.33%,(r=0.96, p<0.01). Complete entrainment of intestinal slow waves wasachieved in every dog with IES using intraluminal ring electrodes. Theeffective stimulation parameters were pulse width of 70 ms, amplitude of4mA and frequency of 1.1xIF.

Example 2

Synchronized IES stimulates intestinal motility and accelerates transitin dogs in a hypomotility model.

Aim: To investigate effects of synchronized IES (SIES) on smallintestinal motility in dogs.

Methods: Seventeen dogs were equipped with a duodenal cannula for themeasurement of small bowel motility using manometry. An additionalcannula was placed in six of the dogs at 1.5 m distal to the first onefor the measurement of intestinal transit. Two pairs of bipolarelectrodes were implanted on the proximal intestine; one for stimulationand the other for recording slow waves. Glucagon (2.87×10−2 μmol/kg) wasused to induce postprandial hypomotility. Pulse trains were used forSIES with the following parameters: train on-time of 0.5 s, pulsefrequency of 20 Hz, pulse width of 2 ms and amplitude of 4 mA and eachtrain of pulses was delivered at the detection of intestinal slow wavepeak.

Results: 1) SIES induced small intestinal contractions during phase I ofthe migrating motor complex. (Contractile index or CI: 5.2±0.6 atbaseline vs. 10.3±0.7 with SIES, P=0.003) 2). In the fed state, SIESsignificantly improved glucagon-induced hypomotility (CI: 3.4±0.5 vs.6.0±0.3, P=0.03) 3). SIES significantly accelerated small intestinaltransit delayed by glucagon (70.4±3.1 min vs. 44.5±3.1 min, P<0.01). 4).There was a negative correlation between the contractile index andtransit time (r=−0.427, p=0.048). 5) The excitatory effect of SIES wasblocked by atropine. 6) Similar enhancement was noted with SIES usingintraluminal electrodes.

Example 3

IES stimulates intestinal motility and accelerates transit in dogs in adisordered motility model

Aim: To study the effects of serosal and intraluminal IES onpostprandial small intestine contractions in a model of dysmotility.

Methods: This experiment was performed in six dogs implanted with dualcannulas in the small intestine with an interval of 150 cm. A nitricoxide synthesis inhibitor, nitro-L-arginine (L-NNA) was used to inducedisordered and spastic (hypertensive) intestinal motility. The studyconsisted of four randomized sessions on separate days with an intervalof at least 2 days: session 1(L-NNA), session 2 (L-NNA plus serosalIES), session 3 (L-NNA plus intraluminal IES) and session 4 (controlsession), In the L-NNA session, after an overnight fast each dog was fedwith 237 ml liquid. Then L-NNA (5 mg/kg) in 20 ml saline was infusedintravenously for 20 min. Small bowel contractions were measured duringthe entire session using a manometric system. Sessions 2 and 3 were thesame as the L-NNA session except that IES was initiated at the time whenL-NNA was given and continued until the end of the experiment. Insession 2, IES was performed using the proximal pair of serosalelectrodes, whereas in session 3, IES was conducted via a pair ofintraluminal ring electrodes attached to the tip of the manometriccatheter that was inserted into the small intestine via the proximalcannula. The control session was identical to the L-NNA session exceptthe replacement of L-NNA with saline. IES was performed using followingparameters (pulse trains): train on-time of 0.5 s and off-time of 2.5 s,pulse frequency of 20 Hz, pulse width of 2 ms, and amplitude of 4 mA.Intestinal transit was measured in the same dogs using a 10-ml solutionof phenol red (0.5 mg/ml) mixed with 1.5% methylcellulose was injectedinto the intestine (distal direction) through the proximal intestinecannula for the assessment of intestine transit.

Results: The motility index was 9.0±0.8 in the control session andincreased to 21.0±2.3 (P=0.001) after L-NNA. The correspondingintestinal transit time was increased from 31.7±6.1 minutes in thecontrol session to 49.0±6.2 minutes with L-NNA (P=0.003). Serosal andintraluminal IES reduced intestine dysmotility and acceleratedintestinal transit. The motility index was reduced from 21.0±2.3 in theL-NNA session to 15.1±1.6 during intraluminal IES (P=0.004) and 14±2.4during serosal IES (P=0.001). No difference was noted in the motilityindex between intraluminal IES and serosal IES (P=0.28). Interestingly,both intraluminal and serosal IES accelerated small intestine transit.The intestinal transit time was reduced from to 49.0±6.2 min in theL-NNA session to 17.7±3.4 min in the intraluminal IES session (P=0.006)and 27.5±6.3 min in the serosal IES session (P=0.02). These values withIES were comparable to that in the control session, suggesting anormalization of intestinal transit. No significant difference was notedbetween serosal IES and intraluminal IES.

All patents, patent applications, and published references cited hereinare hereby incorporated by reference in their entirety. While thedevices and methods of the present disclosure have been described inconnection with the specific embodiments thereof, it will be understoodthat they are capable of further modification. Furthermore, thisapplication is intended to cover any variations, uses, or adaptations ofthe devices and methods of the present disclosure, including suchdepartures from the present disclosure as come within known or customarypractice in the art to which the devices and methods of the presentdisclosure pertain, and as fall within the scope of the appended claims.

What is claimed is:
 1. A system for relieving ileus comprising: one ormore capsules, wherein the one or more capsules include at least oneelectrode pair; a sensing system in communication with the at least oneelectrode pair to receive a sensing information; and an energy deliverysystem in communication with the at least one electrode pair and thesensing system, the energy delivery system being configured to deliverenergy to a patient through the at least one electrode pair based on thesensing information from the sensing system.
 2. The system of claim 1wherein the sensing system and the energy delivery system are embeddedin the one or more capsules.
 3. The system of claim 1 further comprisingan external controller.
 4. The system of claim 3 wherein the one or morecapsules include Bluetooth communication circuitry for communicationwith the external controller.
 5. The system of claim 3 wherein the oneor more capsules includes an antenna for communication with the externalcontroller.
 6. The system of claim 1 wherein the one or more capsulesinclude an attachment mechanism to attach the one or more capsules to aduodenum of the patient.
 7. The system of claim 6 wherein the attachmentmechanism is selected from the group consisting of a barb, a staple, andan adhesive.
 8. The system of claim 1 wherein the energy delivery systemis configured to deliver a single pulse of 100 msec at 4 mA in phasewith natural electrical activity.
 9. The system of claim 1 wherein theenergy delivery system is configured to deliver a pulse train of 20 hzat 1-10 mA in phase with natural electrical activity, with a pulse widthof 2 msec and duration of 500 msec.
 10. The system of claim 1 whereinthe energy delivery system is configured to deliver between 12 to 30pulses per minute out of phase with natural electrical activity, thepulses being of 20 Hz at 4 mA, with a pulse width of 2 msec and durationof 500 msec.
 11. The system of claim 1 where the at least one electrodepair comprises at least one first electrode pair configured to detectthe sensing information and at least one second electrode pairconfigured to provide stimulation energy.
 12. A method for treatment ofgastric motility issues comprising: placing one or more capsules along aduodenum of a patient, wherein the one or more capsules include one ormore electrode pairs; sensing information about motility of a patientfrom the one or more electrode pairs; determining a type of motility thepatient has based on the sensed information; and based on the determinedtype of motility, communicating with the one or more electrode pairs inthe duodenum of the patient to deliver an electrical modulation energyto the patient, wherein a synchronous electrical modulation is appliedif hypomotility is detected and an inhibitory electrical modulation isapplied if uncoordinated hypermotility is detected.
 13. The method ofclaim 12 wherein the one or more capsules include Bluetoothcommunication circuitry for communication with an external controller.14. The method of claim 12 wherein a sensing system for sensinginformation and an energy system for delivering energy are embedded inthe one or more capsules.
 15. The method of claim 12 further comprisingan external controller.
 16. The method of claim 12 wherein the step ofcommunicating comprises delivering a single pulse of 100msec at 4mA inphase with natural electrical activity.
 17. The method of claim 12wherein the step of communicating comprises delivering a pulse train of20 hz at 1-10 mA in phase with natural electrical activity, with a pulsewidth of 2 msec and duration of 500 msec.
 18. The method of claim 12wherein the step of communicating comprises delivering between 12 to 30pulses per minute out of phase with natural electrical activity, thepulses being of 20 Hz at 4 mA, with a pulse width of 2 msec and durationof 500 msec.
 19. The method of claim 12 wherein the one or more capsulescomprises a plurality of capsules placed along the duodenum of thepatient.
 20. The method of claim 12 further comprising a step ofsecuring the one or more capsules to the duodenum of the patient.